Dementia is a progressive disorder characterised by memory loss and impaired cognitive ability. It has been defined as a decline in memory with impairment of at least one other cognitive function, such as skilled movements (limb apraxia), language (aphasia) or executive function (e.g. planning, attention and abstract reasoning). The decline appears as a noticeable change in behaviour and typically impairs social and/or occupational functioning. The condition is distinct from memory loss and cognitive decline associated with other psychiatric conditions such as depression, mood disorders or psychosis.
Dementia comes in many forms and has many causes. The most common forms of dementia are dementia associated with Alzheimer's disease, Lewy body dementia and vascular dementia arising from cerebrovascular injuries such as stroke.
Alzheimer's disease is by far the most common type of dementia and is estimated to account for 60% to 80% of all cases. Patients suffering from Alzheimer's disease typically initially experience insidious memory loss and focal cognitive dysfunction. This is followed by progressive deterioration of cortical functions such as language, visuospatial tasks, abstract reasoning, calculating, left-right disorientation and/or limb praxis. Motor skills such as walking are generally preserved. The onset of Alzheimer's disease typically occurs after 45 years of age but is more common after 65 years of age.
Alzheimer's disease is determined by clinical diagnosis. There is currently no definitive laboratory test that can be carried out on a live patient which can confirm the presence of the condition, although brain imaging such as tomography or magnetic resonance imaging can contribute towards a diagnosis.
Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. The disease is associated with the accumulation of neuritic plaques (amyloid plaques) and neurofibrillary tangles in the brain. The amyloid plaques are made up from amyloid-β, small peptides 39-43 amino acids in length that are fragments of a larger protein amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP is critical to neuron growth, survival and post-injury repair but, in Alzheimer's disease, an unknown process causes APP to be divided into smaller fragments, one of which consists of amyloid-β fibrils. The amyloid-β fibrils form clumps that deposit around the neurons in dense formations as plaques. The neurofibrillary tangles are caused by hyperphosphorylation of tau protein.
Lewy body disease, a synucleinopathy, is second only to Alzheimer's disease in prevalence and symptoms include deficits in attention and concentration, reduced verbal fluency, difficulty in performing visuospatial tasks and psychomotor slowing, as well as parkinsonism. The disease is characterised by the accumulation of insoluble neuronal inclusions known as Lewy Bodies, formed predominantly from insoluble α-synuclein, in the cortical and subcortical regions of affected individuals.
Vascular dementias account for about 10-20% of dementia cases and typically arise as a consequence of a cerebrovascular disease resulting in stroke(s).
Other forms of dementia include those associated with or arising from tauopathies such as Pick's disease and prionopathies such as Creutzfeldt-Jakob disease and new variant Creutzfeldt-Jakob disease.
Further information on the various types of dementia may be found in the reviews by Bradley F. Boeve, “A Review of the Non-Alzheimer's Dementias, J. Clin. Psychiatry, 2006; 67: 1985-2001 and Kevin R. Scott et al., “Dementia syndromes: evaluation and treatment”, Expert Rev. Neurotherapeutics 7 (4), 2007, 407-422 and references cited therein.